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In: Leukemia & Lymphoma, Informa UK Limited, Vol. 45, No. 12 ( 2004-12-01), p. 2455-2458

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428190400005346

Language: English

Publisher: Informa UK Limited

Publication Date: 2004

detail.hit.zdb_id: 2030637-4

In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 880-880

Abstract: Treatment of elderly patients (pts) with AML requires a sensitive balance between efficacy and toxicity. In the AML97 study all pts with AML 〉 60 years (y) were registered and, according to their clinical status, treated in curative, palliative or supportive intention. From a total of 520 pts enrolled, 375 (72%) pts were allocated to the curative, 112 (22%) to the palliative and 33 (6%) to the supportive part of the protocol. Patient characteristics between the 3 groups differed in respect to age, but not in regard to the distribution de novo and secondary AML. Median age of the pts was 66 y (range 60–80 y), 75 y (range 64–90 y) and 76 y (range 63–97 y) for the curative, palliative and supportive protocol respectively. Curative treatment consisted of one (in case of PR after the first chemotherapy of two) courses of induction therapy (AraC 2 g/m2 iv on day (d) 1,3,5,7 in combination with mitoxantrone 10 mg/m2 iv d 1-3) followed by two consolidation courses (AraC 240 mg/m2 iv d 1-5 combined with mitoxantrone 10 mg/m2 iv d 1-2). Palliative treatment included idarubicin 10 mg po d 1 in combination with thioguanine 40 mg po d 1-5, or AraC 80 mg sc d 1-5 or etoposide 100mg po d 1-5. In the supportive arm transfusions were applied. CR was obtained in 75% (95 CI: 68–82%) of pts with de novo AML and in 61% (95 CI: 50–70%) of pts with secondary AML in the curative arm with an early death rate of 12 % (95CI: 7–17%) and 19% (95 CI: 12–24%) respectively. Cytogenetic risk factors at diagnosis were the most important prognostic factor for CR (p 〈 0,0005, multivariate analysis). Pts with favourable karyotype achieved CR in 93%, with normal in 80 %, with other aberrations in 79% and with unfavourable karyotype in 46%. The overall survival (OS) after 2 years in the curative part of protocol was 0,31 ± 0,03 for all pts. With a median follow up of 283 d (range 33 – 1688) the actual OS was 0,58 ± 0,15, 0,38 ± 0,06, 0,39 ± 0,09 and 0,14 ± 0,05 for pts with favourable, normal, other and unfavourable cytogenetics respectively. Interestingly age was not an important determinant, even if results were analysed in a cohort of 603 pts with AML of any age with a similar induction therapy. CR rates of pts below and above 60 y were identical, if they were stratified by cytogenetic risk factors. Median survival was 54 d and only 12 d for pts treated with palliative chemotherapy and supportive therapy respectively. We conclude, that the curative protocol is able to induce high CR in pts with AML 〉 60 y with low mortality and CR are not different to those of pts 〈 60 y, if cytogenetics are taking into account. Despite high CR rate, OS remains low and consolidation therapy need to be improved. Transplant protocols with reduced intensity conditioning are currently tested in these patients. Treatment results in the palliative arm are disappointing and confirm the need to develop novel therapeutic strategies.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V104.11.880.880

Language: English

Publisher: American Society of Hematology

Publication Date: 2004

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2596-2596

Abstract: Background: Promising results have been observed in our previous phase-II study evaluating the combination of Bendamustine plus Rituximab (B-R) in patients with relapsed/refractory indolent or mantle cell lymphomas. An overall response rate (ORR) of 90%, including a 60% rate of complete remissions (CR) was documented. Objective: In October 2003, we initiated a multicenter randomized phase-III study to compare efficacy and safety of the combination B-R versus CHOP plus Rituximab (CHOP-R) as first-line therapy for follicular, indolent and mantle cell lymphomas. Methods: Patients (pts) were randomized to receive Rituximab 375 mg/qm (day 1) plus either Bendamustine 90 mg/qm (days 1+2) every 28 days or the standard CHOP regimen every 21 days for a maximum of 6 cycles. The primary endpoint was event-free survival (EFS). The trial was calculated to power the study to demonstrate a non-inferior EFS associated with B-R treatment, as defined by a difference in EFS between the two regimes of less than 10% after 3 years. An event was defined by a response less than a partial response, disease progression, relapse, or death from any cause. The study is closed according to the planned recruitment schedule. Results: 546 patients have been randomized. For this second interim analysis, 437 patients are evaluable for response (B-R: n=221; CHOP-R: n=212). Median patient age is 64 years. Histologies are equally distributed between arms: follicular 52%, mantle cell 20%, and other indolent lymphomas 28% in both treatment groups, each. The ORR for pts treated with B-R was similar to that associated with CHOP-R (94% vs 93%, respectively). CR was also similar at 41% for B-R compared to 33% for CHOP-R. The median follow-up time for both groups is 28 months. Thus far, 50 deaths have been observed (B-R: 25; CHOP-R: 25). Progressive or relapsed disease has been documented during the follow-up period: 58 in pts treated with B-R and 75 in the CHOP-R group. The median EFS for B-R is not yet reached, the median EFS for CHOP-R is 39 months with no statistical significant difference for the EFS between both groups. The B-R regimen appears to have a better toxicity profile, as evidenced by a lower rate of total alopecia (0% with B-R vs. 89% CHOP-R) and a lower number of infectious complications (number of patients with infections of any grade were 56 (25%) in the B-R group vs. 78 (37%) in CHOP-R group). Correlating, the CHOP-R regimen was more hematotoxic: WHO grade 3/4 leukocytopenia was reported in 36% CHOP-R treated pts compared with 19% in pts treated with B-R, while in the CHOP-R group more frequently G-CSF was used. Conclusions: In this second interim analysis, the combination of Bendamustine plus Rituximab appears to be non-inferior to the standard CHOP-R while showing a better tolerability profile. Further updated results will be presented at this time.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.2596.2596

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4485-4485

Abstract: Introduction The inclusion of "novel" agents including proteasome inhibitors or IMiD-derivatives in the treatment of multiple myeloma significantly improves patient survival. Results of several study groups suggest incorporating at least one "novel agent" in first-line treatment before and after high-dose chemotherapy (HDT) followed by autologous stem cell transplantation. Here we address four main questions: First, what determines (excellent) long-term survival for different treatment regimen? Second, can we show benefit of novel agents for all patients and molecular subentities, including low risk? Third, can the prognostic impact of molecular entities be explained by different association with response, proliferation, and renal impairment? Fourth, does it matter regarding long-term survival by which agents, i.e. "old" vs. "new", a response was reached? Patients and Methods Patients were included in the prospective phase III HOVON-65/GMMG-HD4-trial (German part, n=354) randomizing VAD-induction, autologous tandem-transplantation and thalidomide-maintenance vs. PAD-induction, tandem-transplantation and bortezomib-maintenance. Plasma cells after CD138-purification were subjected to interphase fluorescence in-situ hybridization and gene expression profiling using Affymetrix U133 2.0 DNA-microarrays. Median follow-up (time to censoring) was 93 months. Results Low proliferation, revised-ISS I and cyto-ISS I delineate excellent long-term survival (70-75% after eight years, both arms). Molecular entities are associated with proliferation-rate, i.e. higher (del17p13, del8p21, del13q14, 1q21+, t(4;14)) or lower proliferation (hyperdiploidy), and response: bad response/survival in case of del17p, bad response/no survival impact (t(11;14)), and good response/bad survival (1q21+, t(4;14), and del13q), depending on the treatment regimen. Thus, it does not hold true that good response = good survival if patients are substratified according to their molecular background. Renal insufficiency is associated with 1q21+, del17p13, and t(4;14). For patients with ≥1 of the chromosomal aberrations del17p13, t(4;14), 1q21+ (i.e. cytogenetic high risk, 27.5% of patients) or renal insufficiency (10.6%), risk is abrogated; in absence of these risk features, no benefit could be shown. Patients reaching a near complete remission or better (≥nCR) with VAD-based regimen, HDT followed by thalidomide maintenance show significantly better survival compared to those reaching ≥nCR after bortezomib-based induction/HDT followed by bortezomib maintenance treatment. Conclusions Taken together, adversely prognostic molecular entities are associated with proliferation but can show association with better or adverse remission. Bortezomib-based upfront treatment abrogates chromosomal high-risk aberrations and renal insufficiency; however, no long-term survival-benefit is evident for those without these risk factors or low proliferation, i.e. the majority of patients. Responses achieved by different regimen are not equal in transmission in long-term survival. Responses (≥nCR) are not equivalent regarding their biological and prognostic role in patients with different molecular background and different treatment regimen. Disclosures Seckinger: Celgene: Research Funding; Sanofi: Research Funding; EngMab: Research Funding. Salwender:Novartis: Honoraria, Other: travel suppport, Research Funding; Amgen: Honoraria, Other: travel suppport, Research Funding; Bristol-Myers Squibb: Honoraria, Other: travel suppport, Research Funding; Celgene: Honoraria, Other: travel suppport, Research Funding; Takeda: Honoraria; Janssen: Honoraria, Other: travel support, Research Funding. Scheid:Celgene: Honoraria; Janssen: Honoraria. Knauf:Janssen: Consultancy; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; Gilead Sciences: Consultancy; Roche: Consultancy; Amgen: Consultancy, Honoraria; Mundipharma: Consultancy. Duehrsen:AbbVie: Consultancy, Honoraria; Amgen: Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Consultancy, Honoraria. Dürig:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; Celgene: Honoraria. Schmidt-Wolf:Janssen: Research Funding; Novartis: Research Funding. Haenel:Novartis: Honoraria; Amgen: Honoraria; Roche: Honoraria; Takeda: Honoraria. Raab:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Sonneveld:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Blau:Celgene: Other: Advisory board, Research Funding; Janssen: Other: Advisory board, Research Funding; Amgen: Other: Advisory board; Takeda: Other: Advisory board; Novartis: Other: Advisory boards; BMS: Other: Advisory board. Hillengass:Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Celgene: Consultancy, Honoraria, Other: Advisory Board, Research Funding; amgen: Consultancy, Honoraria, Other: Advisory Board; Sanofi: Research Funding; Janssen: Honoraria, Other: Advisory Board; Novartis: Honoraria, Other: Advisory Board. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldschmidt:Chugai: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Mundipharma: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; ArtTempi: Honoraria. Hose:Celgene: Honoraria, Research Funding; EngMab: Research Funding; Sanofi: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-113284

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Der Onkologe, Springer Science and Business Media LLC, Vol. 28, No. S1 ( 2022-02), p. 19-22

Type of Medium: Online Resource

ISSN: 0947-8965 , 1433-0415

URL: Article

DOI: 10.1007/s00761-022-01106-x

Language: German

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 3120761-3

detail.hit.zdb_id: 1462966-5

In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 97, No. 12 ( 2018-12), p. 2437-2445

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-018-3449-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2018

detail.hit.zdb_id: 1458429-3

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4779-4779

Abstract: Background High quality response [very good partial remission (VGPR), complete remission (CR)] is associated with improved long-term outcome in multiple myeloma (MM) therapy. Lenalidomide (Len)/ dexamethasone (Dex) (Rd) is considered a standard 2nd-line regimen. However, after 1st-line MM therapy containing a “novel agent” like thalidomide, only a relatively small fraction (21.3%) of patients (pts) achieved VGPR or better when RD was used in relapsed/refractory MM (RRMM)1. Bendamustine (Ben) is an alkylating agent with superior activity compared to melphalan/prednisone. The combination of Ben, Len and Dex (BRd) in pts with advanced RRMM resulted in dose-limiting hematotoxicity, which restricted its efficacy in extensively pretreated pts2. However, recent phase I experience demonstrated the feasibility of BRd as 2nd- and 3rd-line myeloma therapy3. We therefore evaluated the efficacy and toxicity of the BRd-regimen as 2nd line therapy for RRMM. Patients and methods This multicenter Phase II study was designed to enroll 50 pts with RRMM undergoing 2nd-line MM therapy [including also pts with prior autologous stem cell transplantation (ASCT)]. Pts had to have measurable disease, ECOG performance status 0-2, adequate hematological values and a creatinine clearance 〉 50 ml/min. Study treatment consisted of Ben 75 mg/m2 i.v. day (d) 1 & 2 and Len 25 mg p.o. d 1-21 for a total of six 28-day induction cycles. Dex (40 and 20 mg p.o. for pts 〈 = or 〉 75 years of age, respectively) was given on d 1, 8, 15, and 22. Pegfilgrastim 6 mg s.c. was administered on d 3 in case of severe neutropenia, treatment delay due to neutropenia or febrile neutropenia according to predefined application rules. Induction treatment was followed by 12 cycles (28 d) of maintenance therapy with Rd at the same dose. The primary study endpoint was the CR/VGPR rate after induction therapy, based on standard IMWG criteria. A Simon's two stage design was used to differentiate between 20% (considered uninteresting) vs 40 % (considered promising, power of 80%, p=5%) of high quality responses. At least 13 pts with VGPR or better after induction therapy were required to meet the statistical threshold predefined for promising activity of the BRd regimen in this study. Results 50 pts were enrolled between 04/2012 and 07/2014 (median age 68 years [46-84y], 73% men). 49% pts had ISS stage II/III, 42.5% had undergone prior SCTs, and 13% had known high risk cytogenetic aberrations. 91% of pts had received novel agents (thalidomide, bortezomib) during 1st-line therapy. At the time of abstract submission, data from 38 pts having completed induction treatment were available. Final analysis of the primary study endpoint including all patients will be updated and presented at the meeting. Of the currently 38 evaluable pts, 20 (52.6%, Table 1) achieved a CR/VGPR after a median of 3.3 induction cycles. Only 1 patient experienced disease progression (PD) during induction phase. 77% of pts received pegfilgrastim. Dose reduction during induction therapy was required in 7.7% of pts. 42.5% received 〈 6 scheduled induction cycles (50% due to toxicities, 50% for other reasons). 49% had treatment-related SAEs. Grade 3/ 4 neutropenia and thrombocytopenia occurred in 51%/25.5% and 23.4%/8.5% of pts, respectively. Only 1 patient developed CTC grade 3 febrile neutropenia. Most common grade 3/4 non-hematologic toxicities were infections (14%), rash (9.5%), and diarrhea (9.5%). Anaphylactic reaction grade 4 related to Ben and pulmonary embolism grade 3 occurred in 1 patient each. A cerebral insult grade 4 occurred in a patient non-compliant with the anti-thrombotic prophylaxis required per protocol. One death due to respiratory failure (considered to be unlikely related to study treatment) was reported for an 83 year old male. Conclusion BRd is a safe and efficacious regimen for 2nd line treatment of RRMM patients whose 1st-line therapy included thalidomide or bortezomib. High quality responses ( 〉 = VGPR) can be achieved in a considerable proportion (52.6%) of these pts. Our study suggests that the fraction of patients achieving VGPR or better after BRd treatment may be substantially higher than attainable with Rd alone. References 1 Wang et al. Blood, 2008, 112: 4445-51 2 Lentzsch et al. Blood, 2012, 119: 4608-13 3 Poenisch et al., Br J Haematol, 2013, 162, 202–9 Table 1 Best response after induction CR VGPR PR MR SD total (n=38) 3 17 15 1 2 prior ASCT (n=16) 2 6 7 1 0 no prior ASCT (n=22) 1 11 8 0 2 Disclosures Mey: Mundipharma: Honoraria, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Use of Bendamustine in relapsed/refractory Multiple Myekoma. To investigate the efficacy and safety of Bendamustine in combination with the standard backbone of Lenalidomide/ Dexamethasone in patients with replaced/refractory MM.. Bargetzi:Celgene: Membership on an entity's Board of Directors or advisory committees. Taverna:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Schmid:Celgene: Honoraria. Knauf:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. von Moos:Amgen: Consultancy, Honoraria, Research Funding. Hiendlmeyer:Celgene: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding. Hitz:Celgene: Research Funding. Driessen:Mundipharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.4779.4779

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Digestion, S. Karger AG, Vol. 23, No. 3 ( 1982), p. 174-183

Type of Medium: Online Resource

ISSN: 0012-2823 , 1421-9867

URL: Article

DOI: 10.1159/000198725

Language: English

Publisher: S. Karger AG

Publication Date: 1982

detail.hit.zdb_id: 1482218-0

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 35, No. 5-6 ( 1999-01), p. 641-642

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428199909169633

Language: English

Publisher: Informa UK Limited

Publication Date: 1999

detail.hit.zdb_id: 2030637-4

In: European Journal of Haematology, Wiley, Vol. 108, No. 2 ( 2022-02), p. 133-144

Abstract: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low‐dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real‐world evidence is scarce. Patients and Methods POSEIDON was a prospective non‐interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians’ choice. Data were analyzed descriptively. Results Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression‐free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1] . Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. Conclusion The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real‐world setting. Registered at clinicaltrials.gov (NCT02075996).

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.v108.2

DOI: 10.1111/ejh.13719

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2027114-1